Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) is used to create applications for surfactants and paper, packaging, and surface (eg, carpets, textiles) protectants. Such POSF-based products or their residuals may degrade or metabolize to PFOS (C8F17SO3−). PFOS concentrates in liver and serum and results in hypolipidemia as an early effect of cumulative dosages. Male and female employees of two perfluorooctanyl-manufacturing locations (Antwerp, Belgium and Decatur, Alabama) participated in a periodic medical surveillance program that included hematology, clinical chemistry, thyroid hormone, and urinalysis testing. Serum concentrations of PFOS and perfluorooctanoate (PFOA, C7F15CO2−, used as a fluoropolymer emulsifier) were measured via mass spectrometry methods. The mean serum PFOS and PFOA concentrations for 263 Decatur employees were 1.32 parts per million (ppm; geometric mean 0.91, range 0.06–10.06 ppm) and 1.78 ppm (geometric mean 1.13, range 0.04–12.70 ppm), respectively. Mean concentrations were approximately 50% lower among 255 Antwerp workers. Adjusting for potential confounding factors, there were no substantial changes in hematological, lipid, hepatic, thyroid, or urinary parameters consistent with the known toxicological effects of PFOS or PFOA in cross-sectional or longitudinal analyses of the workers’ measured serum fluorochemical concentrations.